Synthesis of α‑l‑Threose Nucleoside Phosphonates via Regioselective Sugar Protection

A new synthesis route to α-l-threose nucleoside phosphonates via 2-O and 3-O selectively protected l-threose is developed. The key intermediates 2-O-benzoyl-l-threonolactone and 1-O-acetyl-2-O-benzoyl-3-O-t-butyldiphenylsilyl-l-threofuranose were functionalized to synthesize 2′-deoxy-2′-fluoro- and 3′-C-ethynyl l-threose 3′-O-phosphonate nucleosides. The key intermediates developed are important intermediates for the synthesis of new l-threose-based nucleoside analogues, TNA phosphoramidites, and TNA triphosphates.